tbuckley/cabot-search huggingface dataset:
A phase 1/2 study of RTX-224, an engineered red blood cell expressing 4-1BB ligand and membrane-bound IL-12, for the treatment of patients with select advanced solid tumors.
Authors: Alexander I. Spira, Melissa Lynne Johnson, Ai Ren, Varsha Sundaresan, Ines Verdon, Laurence Turka, Sivan Elloul
Journal: Journal of Clinical Oncology (2022)

TPS2680 Background: RTX-224 is a genetically engineered off-the-shelf, allogeneic red blood cell that expresses the costimulatory molecule 4-1BB ligand (4-1BBL) and cytokine interleukin-12 (IL-12) on the cell surface. The use of 4-1BB and IL-12 agonists for cancer immunotherapy has been limited due to systemic toxicities. Unlike agonist antibodies and recombinant cytokines, which are distributed systemically, Red Cell Therapeutics, such as RTX-224, are restricted to the vasculature and spleen, which may limit toxicities previously observed with agonist 4-1BB monoclonal antibodies and recombinant IL-12. RTX-224 is designed to be a broad immune agonist of both adaptive and innate responses that activates and expands effector and memory CD8+ and CD4+ T cells, cytotoxic natural killer (NK) cells and produces inflammatory cytokines and chemokines, leading to enhanced antigen presentation. In preclinical studies, the combined activation of both adaptive and innate immune responses by the murine surrogate of RTX-224 led to antitumor activity while the restricted biodistribution improved the safety profile. Methods: The RTX-224-01 study is a Phase 1/2, first-in-human, multi-center, dose-escalation and expansion study of RTX-224 in patients with relapsed or refractory urothelial cancer, squamous cell carcinoma of the head and neck, non-small cell lung cancer, triple negative breast cancer and cutaneous melanoma. Safety, tolerability, pharmacokinetics and pharmacodynamics and anti-tumor activity of RTX-224 will be assessed. Approximately 28 patients will be enrolled across dose level cohorts to identify the recommended Phase 2 dose (RP2D). The starting dose is 100 million (1x10 8 ) cells administered intravenously every 3 weeks (Q3W) and the dose will be escalated by half-log increments following a Bayesian logarithmic regression model (BLRM) with overdose control. Following RP2D selection, each of the 5 expansion cohorts will enroll approximately 20 patients. Pharmacodynamic and exploratory biomarker studies correlative to clinical response will be evaluated on peripheral blood and paired tumor biopsies. Multiple technologies will be employed to profile the innate and adaptive responses following RTX-224 treatment. The study is open and enrolling patients in Phase 1. Clinical trial information: NCT05219578.
Adaptive expertise for medical oncology fellows: How to foster evidence-based medicine mastery.
Authors: Parul Agarwal, Linda Regan, Ross C. Donehower, Kristen Marrone
Journal: Journal of Clinical Oncology (2022)

e23015 Background: Adaptive expertise (AE) describes a physician’s ability to effectively apply pre-existing knowledge to unfamiliar clinical situations. This skill relies on understanding not just “how” solutions work, but instead developing a framework of “why” a specific decision is correct for a particular situation. Acquiring this skillset enables one to rely on foundational knowledge, while simultaneously reaching for novel information in order to make the best clinical decision. Given the expansion of primary literature and evolving treatment options in oncology, development of AE is critical for fellows to provide high level patient care. There is limited research focused on oncology trainee development of AE and evidence-based medicine (EBM) mastery. Methods: We designed an observational cohort study of ten first-year medical oncology fellows at Johns Hopkins during the 2021-2022 academic year (IRB00293232). Fellows were required to attend a case-based, faculty moderated EBM peer-teaching curriculum. A validated, ten question Likert scale AE questionnaire (Carbonell instrument) was administered to each fellow at baseline. Data collection from weekly questionnaires measuring efficiency and innovation in case preparation and presentation is ongoing. These data will be quantitatively summarized and correlated with the baseline AE instrument to evaluate change and development of AE over the academic year. Results: Ten learners have participated in the curriculum as of February 2022. All questions in the baseline AE instrument had a 100% response rate. Selected results are presented in Table.While all participants “strongly agree” that knowledge in their discipline keeps on developing, only 50% “strongly agree” that they are able to apply knowledge in new and unfamiliar situations with a degree of success, highlighting the need for a curriculum focused on AE for trainees. Conclusions: AE utilizing EBM in medical oncology is an essential skill for trainees to acquire. Next steps will include moderated focus groups at the 6 month and 10-month time point, followed by analysis of the weekly questionnaires, which will allow for formal assessment of this curriculum. Future directions will include expansion to include other institutions and adaption for different learner levels.[Table: see text]
Distinct oncogenic signatures in malignant PEComa and leiomyosarcoma identified by integrative RNA-seq and H3K27ac ChIP-seq analysis.
Authors: Krinio Giannikou, Ahmad-Abdel Azim, Elio Adib, Inga-Marie Schaefer, Nikolas Kesten, Len Taing, Zachary Zhu, Jason Hornick, Michelle S. Hirsch, Henry Long, Andrew J. Wagner, Matthew Louis Hemming, David J. Kwiatkowski
Journal: Journal of Clinical Oncology (2022)

11552 Background: Malignant perivascular epithelioid cell tumor (PEComa) and leiomyosarcoma (LMS) are two sarcomas with overlapping morphologic and immunophenotypic features which can make their diagnostic distinction challenging. We aimed to characterize the transcriptional and epigenetic landscape of PEComa and LMS to identify distinguishing features. Methods: We performed whole transcriptome RNA-sequencing on 19 PEComas and compared their gene expression profile to 259 sarcomas from The Cancer Genome Atlas (TCGA) including 104 LMS. ChIP-sequencing for H3K27ac, a histone modification associated with activation of nearby genes/open chromatin, was conducted on 9 malignant PEComas and 12 LMS and were compared with publicly available data from 4 other sarcoma subtypes (chordoma; osteosarcoma; undifferentiated pleomorphic sarcoma; rhabdomyosarcoma; n = 29 tumors). Results: Genome-wide epigenetic and transcriptional analyses revealed overlapping patterns between PEComa and LMS, which were distinct from other sarcomas. However, we also identified a set of highly expressed and epigenetically distinct transcripts which may represent diagnostic?biomarkers: e.g., DAPL1, MLANA, SULT1C2, GPR143, and CHI3L1 for PEComa; and MYOCD, WDFC2, DES, MYH11, and CNN1 for LMS; each of which showed &gt;17x fold higher expression for each tumor entity by DESeq2 (FDR&lt;0.0001). Gene Set Enrichment Analyses (GSEA) demonstrated enrichment in the KEGG Lysosome pathway for PEComa (FDR=0.11), whereas myogenesis and smooth muscle contraction pathways were enriched in LMS (FDR=0.09). Integrative transcriptomic and epigenetic analyses revealed a unique set of master core transcription factors for each tumor type including among others MYOCD for LMS; MITF for PEComa, which require further functional investigation. Twelve selected genes including new as well as known and standard diagnostic markers (e.g., DAPL1, MLANA, GPR143, PNL2, CHI3L1, DES, MYH11, ER, CD68, PU.1, pS6 and CNN1) were validated by immunohistochemistry (IHC) in multiple sections from PEComa and LMS (n = 26). The combination of three melanocytic markers (HMB45, MLANA, PNL2) and pS6 can distinguish LMS from PEComas (**** p&lt;0.0001). IHC for CD68 and PU.1 macrophage markers did not show any difference regarding the degree of immune infiltration in PEComa vs. LMS. Conclusions: Our studies revealed novel epigenetic signatures translating into lysosomal and melanocytic proteins for PEComa and myogenic proteins for LMS, which may serve as useful diagnostic biomarkers in the distinction of these two sarcoma subtypes.
Combining stereotactic radiotherapy with anti-PD-1 for advanced hepatocellular carcinoma patients with portal vein tumor thrombus.
Authors: Bin Zhou, Xiangdong Sun
Journal: Journal of Clinical Oncology (2022)

e16121 Background: Immunotherapy has attracted extensive attention in advanced hepatocellular carcinoma. For unselected patients, the efficacy of PD-1 monotherapy is less than 20%. The addition of radiotherapy to local lesions can significantly enhance the effectiveness of PD-1. However, the efficiency of SBRT combined with PD-1 in the treatment for portal vein tumor thrombus in patients with hepatocellular carcinoma remains unclear. Methods: This phase II study enrolled 17 patients with advanced liver cancer with portal vein tumor thrombus after 1-line or multi-line treatment in our single center, between June 2018 and June 2021. SBRT was delivered to the carcinoma thrombus with or without primary intrahepatic tumor，with a median total dose of 60Gy/10fx (range of 50Gỹ70Gy). Camrelizumab was administered within 2 weeks after SBRT, in cycles of every 3 weeks, until disease progression or patient intolerance. The primary endpoints were overall survival (OS), progression-free survival (PFS) and overall response rate (ORR). Results: At 3 months after SBRT, 6 patients had complete responses (35.3%) and 11 patients had partial responses (64.7%), with an ORR of 100%. The 1-year OS rate was 100%, and 1-year PFS was 84.8%. None of the patients had radiation response. Four patients (23.5%) were unable to tolerate immunotherapy, with one patient stopping after 12 cycles due to frequent preventricular phase contraction (in a double couplet rhythm) and 3 owing to upper gastrointestinal bleeding. Conclusions: SBRT combined with immunotherapy can improve local control and bring survival benefit, suggesting that SBRT could be considered in patients with portal vein tumor thrombus in hepatocellular carcinoma after 1-line or multi-line treatment. Moreover, the adverse reactions were mild. Clinical trial information: ChiCTR1900026188.
A first-in-human, phase I, open-label study of a novel cancer vaccine labvax 3(22)-23 and adjuvant GM-CSF in patients with advanced stage adenocarcinomas.
Authors: Weijie Ma, Shuai Chen, Nancy L. Ogihara, Jasmine Huynh, Ariel Yen, Karen Kelly, Primo "Lucky" N. Lara, James A. Radosevich, Michael Babich, Tianhong Li
Journal: Journal of Clinical Oncology (2022)

TPS2700 Background: Adenocarcinoma is the most common histologic type of solid tumors and can arise from almost anywhere in the body. Labyrinthin is a novel tumor-specific protein expressed on the cell surface of the majority of adenocarcinomas of various cancer types. Several therapeutic strategies targeting labyrinthin are under development. We hypothesize that vaccination against labyrinthin can elicit strong immune responses against the labyrinthin-positive adenocarcinomas in cancer patients. LabVax 3(22)-23 is a novel anti-tumor vaccine that contains 4 synthetic labyrinthin-based peptides designed to elicit both B-cell and T-cell responses. Sargramostim, a recombinant granulocyte macrophage colony-stimulating factor (GM-CSF), is given as an immunostimulator with LabVax 3(22)-23 to boost the antitumor immune response. Preclinical studies showed that LabVax 3(22)-23 significantly inhibited tumor growth that was augmented by GM-CSF without any significant toxicity in C57/BL6 transgenic mice expressing human PD-1/PD-L1 implanted with the murine colon adenocarcinoma cell line MC-38-huPD-L1. This single institution, first-in-human, phase I trial (UCDCC#296) evaluates LabVax 3(22)-23 and adjuvant sargramostim in patients with labyrinthin-positive metastatic or recurrent adenocarcinoma of any primary tumor site after all standard-of-care therapies. Methods: The primary objective is to assess the toxicity of LabVax 3(22)-23 and adjuvant sargramostim according to NCI CTCAE V5.0. The primary endpoint is dose limiting toxicity (DLT), which is defined as grade ≥ 2 allergic and autoimmune reaction, grade ≥ 3 injection site reaction, any grade 3 toxicities lasting &gt;1 week, or any grade ≥ 4 toxicities. With a sample size of 10 patients, there is 89-97% of chance to observe ≥1 DLT if the true event rate is 20-30%. A secondary endpoint is the preliminary assessment of tumor response rate by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Exploratory objectives measure the effect of LabVax 3(22)-23 on various immune responses (cytokines, anti-labyrinthin antibody production) and the correlation between the level of labyrinthin expression and the efficacy of LabVax 3(22)-23. Eligible patients are required to have labyrinthin expression on their tumor cells by immunohistochemistry and adequate organ function. Patients receive sargramostim subcutaneously and LabVax 3(22)-23 intradermally on weeks 1, 2, 4, 8, and 12 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 1 year. Two patients are enrolled at the time of submission. Clinical trial information: NCT05101356.
AdvanTIG-206: Anti-TIGIT monoclonal antibody (mAb) ociperlimab (BGB-A1217; OCI) plus anti-programmed cell death protein-1 (PD-1) mAb tislelizumab (TIS) plus BAT1706 versus TIS plus BAT1706 as first-line (1L) treatment for advanced hepatocellular carcinoma (HCC).
Authors: Jia Fan, Zhenggang Ren, Chiun Hsu, Yabing Guo, Tianqiang Song, Wentao Wang, Yee Chao, Yujuan Gao, Vincent Li, Salvatore Ferro, Chia-Jui Yen
Journal: Journal of Clinical Oncology (2022)

TPS4172 Background: Treatment with PD-1/programmed death ligand 1 (PD-L1) inhibitors and anti-angiogenic agents has demonstrated significant survival improvements in patients with untreated HCC. T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a co-inhibitory immune checkpoint receptor upregulated on T cells and natural killer cells in multiple solid tumors. OCI is a novel, humanized mAb that binds TIGIT with high specificity and affinity, blocking interaction with its ligands on tumor cells. TIS is an anti-PD-1 mAb that has demonstrated clinical activity in patients with previously treated, unresectable HCC (NCT03419897). BAT1706 is a similar biological product to the anti-angiogenic agent bevacizumab. OCI combined with TIS and BAT1706 could further enhance both anti-angiogenic and anti-PD-1 therapies for patients with HCC. Methods: AdvanTIG-206 is a Phase 2, randomized, open-label clinical study (NCT04948697). Patients aged ≥ 18 years with histologically confirmed advanced HCC that is not amenable to a curative treatment approach are eligible. Patients must have a Child-Pugh A score, ECOG PS ≤ 1, and have received no prior systemic therapy for HCC. Approximately 90 patients will be randomized 2:1 to OCI 900 mg combined with TIS 200 mg plus BAT1706 15 mg/kg (Arm A) or TIS 200 mg plus BAT1706 15 mg/kg (Arm B), all administered intravenously (once every 3 weeks [Q3W]). The primary endpoint is objective response rate as assessed by the investigator (RECIST v1.1). Radiological assessment of tumor response status will be performed Q6W for the first 48 weeks and Q12W thereafter. Secondary endpoints include duration of response, time to response, disease control rate, clinical benefit rate, and progression-free survival (all by investigator’s assessment), overall survival, safety, pharmacokinetics, and immunogenicity. Study enrollment is ongoing. Clinical trial information: NCT04948697.
Intravenous amisulpride as rescue treatment of postoperative nausea and vomiting in patients undergoing oncologic surgical procedures.
Authors: Amber Elliott, Harold Minkowitz, Claudine Ashburn, Gabriel Fox
Journal: Journal of Clinical Oncology (2022)

12111 Background: Nausea and vomiting or retching after surgery can have significant adverse impacts, including increased length of stay, worse outcomes and patient dissatisfaction. Therefore, effective management remains a high priority. While more aggressive, multimodal prophylaxis has helped, options for treating those patients who fail are limited. Intravenous (IV) amisulpride has been shown to be safe and effective for the rescue treatment of Post-Operative Nausea and Vomiting (PONV) in a large, randomized, double-blind, placebo-controlled trial in a broad surgical population (Habib AS, Kranke P, Bergese SD, Chung F, et al. Anesthesiology 2019;130:203-212). We conducted a post-hoc analysis to investigate the safety and efficacy of amisulpride specifically in those patients undergoing oncologic surgery, predominantly excision of breast, gastrointestinal, or genitourinary malignancies. Methods: This subset analysis includes data from a randomized, double-blind, placebo-controlled, multicenter phase III trial of a single 10 mg dose of IV amisulpride as rescue treatment of PONV occurring in patients failing pre/peri-operative prophylaxis, generally with ondansetron and/or dexamethasone (Habib AS, Kranke P, Bergese SD, Chung F, et al. Anesthesiology 2019;130:203-212). The subset includes only those patients identified as undergoing surgery related to a specified malignancy or a mass considered likely to be malignant. The primary efficacy outcome was complete response (CR), defined as no emetic episodes (vomiting or retching) or administration of antiemetic rescue medication in the 24 hours after dosing. Results: In total, 465 patients were treated with either 10 mg amisulpride or placebo and 112 (56 in each group) underwent oncologic surgery. Of these, 43 (38%) underwent surgery for a pelvic tumor, 37 (33%) had breast or axillary surgery, 13 (12%) had colorectal, hepatic or pancreatic surgery and 19 (17%) underwent procedures for other malignancies, such as nephrectomy or thyroidectomy. The CR rate at 24 hours in the amisulpride group was 38%, compared to 23% with placebo. This was comparable with the success rates for the whole study population (42% vs 29%). The CR rate after 2 hours was 66% in the amisulpride group and 39% in the placebo group, also in line with the overall study results (70% vs 49%). Among those patients whose PONV occurred in the post-anesthesia care unit (PACU), the mean length of PACU stay from treatment to PACU discharge was 156 minutes in the amisulpride group and 230 minutes in the placebo group. Treatment-emergent adverse effects (TEAE) were comparable in nature and incidence between amisulpride and placebo. Conclusions: Amisulpride at 10 mg IV is safe and effective as rescue treatment for PONV in cancer patients undergoing surgery and is associated with a marked reduction in PACU length of stay.
Cost-related medication rationing and nonadherence among Cancer Survivors in the United States.
Authors: Onyema Chido-Amajuoyi, Ikponmwosa Osaghae, Chaitanya Undavalli
Journal: Journal of Clinical Oncology (2022)

e18814 Background: The cost burden associated with cancer care is substantial event. Studies have shown that this burden has continued to increase over time, even for longer term survivors. However, there is a paucity if studies that have described the characteristics of cancer patients who are at greater risk of adopting cost saving behaviors as a means to cope with cancer-related financial burden. Methods: Study data were derived from the 2018 National Health Interview Survey, which is administered annually by the National Center for Health Statistics. Outcomes of interest were reports of medication rationing and nonadherence among cancer survivors who had received a prescription medication from a doctor/health professional in the past 12 months. Survey questions used to assess this were: This was derived via “yes” responses to the survey questions: “DURING THE PAST 12 MONTHS, were any of the following true for you? ...You skipped medication doses to save money” and “DURING THE PAST 12 MONTHS, were any of the following true for you?....you took less medicine to save money”. Survey logistic regressions were used to identify sociodemographic and behavioral factors associated with cost saving behaviors among cancer patients. All analysis were carried using STATA version 14.2'. Results: A total of 2594 cancer survivors were included in our study. Among those who reported skipping medications to save money, 75.5% were females, 29.1% were aged &gt; 65 years, and 50.7% had an annual income &lt; $34,999. Also, 92% had health insurance coverage, 47.5% were never smokers, and 27.3% were current smokers. As income increased, the odds of medication rationing and non-adherence decreased. For example, cancer survivors earning $50,000 - $74,999 were less likely (aOR: 0.49, 95% CI: 0.24-1.00) to skip medications compared to those with income less than $34,999; while those earning $100,000 and over had 83% (aOR: 0.17, 95% CI: 0.07-0.44) lower odds of skipping medications compared to those with income less than $34,999. Compared to cancer survivors with health insurance coverage, those without health insurance coverage were over two folds (aOR: 2.38, 95% CI: 1.07-5.29) more likely to skip medications to save cost. Current smokers were about twice (aOR: 1.98, 95% CI: 1.13-3.48) as likely to skip medications to save money compared to never smokers. Findings with health insurance and cigarette use were constant for medication rationing. Conclusions: From our study, cancer survivors who skip or ration medications are likely to be younger, low-income and have no health insurance coverage. We also found an association between cancer-related cancer saving behaviors and ongoing tobacco use among cancer survivors. These findings align with previous studies and hint at the need for a multipronged approach to minimize the huge cost of treatment incurred by cancer survivors, their families, and the government.